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Composition for regulating cellular senescence comprising [n-2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide

a technology of cyclohexyloxyl and methanesulfonamide, which is applied in the direction of anti-noxious agents, drug compositions, extracellular fluid disorders, etc., can solve the problems of reducing the average lifespan of drosophila or having no effect on the average lifespan, unclear whether the pro-inflammatory activity of cox-2 is involved in the aging process, and the expression of cox-2 is not clear. , to achieve the effect of promoting

Inactive Publication Date: 2012-04-12
SEOUL NAT UNIV R&DB FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about a new discovery that a specific COX-2 inhibitor, called N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide, can regulate cellular senescence in human skin fibroblasts. This discovery is important because it suggests that COX-2 inhibitors may have a wider range of biological effects than previously thought.

Problems solved by technology

However, it is still unclear what the mechanism of aging is.
However, the long-term administration of salicylic acid, acetylsalicylic acid or indomethacin to Drosophila led to a decrease in the average lifespan of the Drosophila or had no effect on the average lifespan (15).
As described above, although various theories for senescence have recently been proposed, it is yet unclear whether the pro-inflammatory activity of COX-2 is involved in the aging process and whether the COX-2 inhibitors can prevent senescence.

Method used

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  • Composition for regulating cellular senescence comprising [n-2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide
  • Composition for regulating cellular senescence comprising [n-2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide
  • Composition for regulating cellular senescence comprising [n-2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide

Examples

Experimental program
Comparison scheme
Effect test

example 1

Cell Culture

[0039]According to the literature of Boyce and Ham (1983), human fibroblasts were isolated from foreskin, and then cultured in a DMEM medium, containing 10% fetal bovine serum (Life Technology Inc., Grand Island, N.Y.), penicillin (100 units / ml) and streptomycin (100 units / ml)). General cultured cells showed a decrease in growth rate with an increase in passage number, and cells with a passage number higher than 30 showed completely arrested growth and started to show characteristic phenomena, such as replicative senescence reported in the prior art (Yeo et al., 2000 a and b).

example 2

Experiment of Regulation of Growth Rate by COX-2 Inhibitors

[0040]In order to examine the effects of COX-2 inhibitors on cellular senescence, cells were treated with each of the three selective COX-2 inhibitors NS-398, celecoxib and nimesulide, the three nonselective COX-inhibitors aspirin, ibuprofen and flurbiprofen, inhibiting the activities of both COX-1 and COX-2, and DMSO (vehicle control group), and then the treated cells were stained using a general cell staining method in the following manner and were measured for population doublings (PDs). First, cells having a number of population doublings (PDs) of 24 were treated with each of DMSO (vehicle control group), NS-398 (20 μM), celecoxib (1 μM), nimesulide (20 μM), aspirin (1 mM), ibuprofen (20 μM) and flurbiprofen (5 μM), and were cultured. Then, the number of the cells was calculated by trypan blue staining, and the number of population doublings (PDs) of the cells was calculated according to the following equation 1:

Number o...

example 3

Senescence-Associated Beta-Galactosidase (SA-β-gal) Staining

[0041]In order to examine the effects of COX-2 inhibitors on cellular senescence, cells were treated with each of the three selective COX-2 inhibitors, NS-398, celecoxib and nimesulide, the three nonselective COX inhibitors aspirin, ibuprofen and flurbiprofen, inhibiting the activities of both COX-1 and COX-2, and DMSO (vehicle control group), and then were subjected to senescence-associated β-galactosidase (SA-β-gal) staining. Herein, the senescence-associated β-galactosidase (SA-β-gal) staining was performed in the following manner according to the method of Dimri et al. (1995) (17). First, cells were treated with each of DMSO (vehicle control group), NS-398 (20 μM), celecoxib (1 μM), nimesulide (20 μM), aspirin (1 mM), ibuprofen (20 μM) and flurbiprofen (5 μM), and were cultured. The cultured cells were seeded on a 35 mm dish, and then stabilized. Then, the cells were washed twice with PBS and fixed with 3% formaldehyde ...

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Abstract

The present invention relates to a composition for inhibiting cellular senescence, comprising N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide.

Description

CROSS-REFERENCE PARAGRAPH[0001]The present application is a divisional of U.S. patent application Ser. No. 12 / 600,447, filed Nov. 16, 2009 (pending), which is a national phase of PCT Application No. PCT / KR2008 / 002688, filed May 14, 2008, which claims the benefit of priority to Korean application number 10-2007-0047015, filed May 15, 2007, the contents of which are incorporated by reference herein in their entirety.TECHNICAL FIELD[0002]The present invention relates to a composition for inhibiting cellular senescence, comprising N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide.BACKGROUND ART[0003]Cellular senescence plays an important role in complex biological processes, including development, aging, and tumorigenesis, and many attempts have been made to understand some of its fundamental features. However, it is still unclear what the mechanism of aging is. Meanwhile, the hypothesis that reactive oxygen species produced in the process of aerobic metabolism damage cells and ar...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/18A61P25/16A61P25/14A61P25/00A61P19/02C12N5/071A61P5/00A61P17/14A61P19/10A61P9/10A61P7/02A61P27/02A61P25/28A61P17/00
CPCA61K31/63A61K31/7076A61K31/70A61P17/00A61P17/02A61P17/14A61P17/16A61P19/02A61P19/08A61P19/10A61P25/00A61P25/14A61P25/16A61P25/28A61P27/02A61P39/06A61P43/00A61P5/00A61P7/02A61P9/10
Inventor PARK, SANG CHULHAN, JEONG A.
Owner SEOUL NAT UNIV R&DB FOUND
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